Extracolonic Cancer Risk After Total Colectomy for Inflammatory Bowel Disease: A Population-based Cohort Study.

炎症性肠病全结肠切除术后结肠外癌症风险: 一项基于人群的队列研究。

  • 影响因子:5.55
  • DOI:10.1093/ecco-jcc/jjz199
  • 作者列表:"Mark-Christensen A","Erichsen R","Veres K","Laurberg S","Sørensen HT
  • 发表时间:2020-06-19

BACKGROUND:Patients with inflammatory bowel disease are at increased risk of extracolonic cancers. Little is known regarding this risk following total colectomy [TC]. METHODS:Patients who underwent TC for inflammatory bowel disease in Denmark during 1977-2013 were identified from the Danish National Patient Registry. Incidence rates of extracolonic cancers were determined through record linkage to the Danish Cancer Registry and compared with expected incidence rates in the general population. Standardized incidence ratios [SIRs] were calculated as the observed vs expected cancer incidence. RESULTS:In total, 4430 patients (3441 with ulcerative colitis [UC]; 989 with Crohn's disease [CD]) were followed for 54,183 person-years after TC. Following their surgery, 372 patients were diagnosed with extracolonic cancer compared to 331 expected [SIR = 1.1 (95% confidence interval {CI}: 1.0-1.2)]. The risk of extracolonic cancer overall was increased among patients with CD and TC (SIR = 1.5 [95% CI: 1.2-1.8]), but not among patients with UC and TC (SIR = 1.0 [95% CI: 0.9-1.2]). Patients with UC and TC had a higher risk of intestinal extracolonic cancer (SIR = 2.0 [95% CI: 1.4-2.7]). Patients with CD and TC had a higher risk of smoking-related cancers (SIR = 1.9 [95% CI: 1.2-2.9]), intestinal extracolonic cancer (SIR = 3.1 [95% CI: 1.6-5.5]) and immune-mediated cancers (SIR = 1.5 [95% CI: 1.0-2.1]). CONCLUSION:Patients with CD and TC had a higher risk of extracolonic cancer overall compared to the general population, while patients with UC and TC did not. Site-specific cancer risk varied according to inflammatory bowel disease type.


背景: 炎症性肠病患者患结肠外癌的风险增加。关于全结肠切除术后的这种风险知之甚少 [TC]。 方法: 在丹麦 1977-2013 期间因炎症性肠病接受 TC 的患者是从丹麦国家患者登记处确定的。通过与丹麦癌症登记处的记录链接确定结肠外癌症的发病率,并与一般人群的预期发病率进行比较。标准化发病率比 [SIRs] 计算为观察到的与预期的癌症发病率。 结果: 总共有 4430 例患者 (3441 例溃疡性结肠炎 [UC]; 989 例克罗恩病 [CD]) 在 TC 后随访了 54,183 人年。手术后,372 例患者被诊断为结肠外癌,预期为 331 [sir = 1.1 (95% 置信区间 {CI}: 1.0-1.2)]。CD 和 TC 患者总体结肠外癌风险增加 (sir = 1.5 [95% CI: 1.2-1.8]),但在 UC 和 TC 患者中不存在 (sir = 1.0 [95% CI: 0.9-1.2])。UC 和 TC 患者患结肠外肠癌的风险较高 (sir = 2.0 [95% CI: 1.4-2.7])。CD 和 TC 患者发生吸烟相关癌症的风险较高 (sir = 1.9 [95% CI: 1.2-2.9]),肠结肠外癌 (sir = 3.1 [95% CI: 1.6-5.5]) 和免疫介导癌 (sir = 1.5 [95% CI: 1.0-2.1])。 结论: 与普通人群相比,CD 和 TC 患者总体上有更高的结肠外癌风险,而 UC 和 TC 患者则没有。部位特异性癌症风险因炎症性肠病类型而异。



来源期刊:The FEBS journal
作者列表:["Sayed IM","Suarez K","Lim E","Singh S","Pereira M","Ibeawuchi SR","Katkar G","Dunkel Y","Mittal Y","Chattopadhyay R","Guma M","Boland BS","Dulai PS","Sandborn WJ","Ghosh P","Das S"]

METHODS::Chronic diseases, including inflammatory bowel disease (IBD) urgently need new biomarkers as a significant proportion of patients, do not respond to current medications. Inflammation is a common factor in these diseases and microbial sensing in the intestinal tract is critical to initiate the inflammation. We have identified ELMO1 (Engulfment and Cell Motility Protein-1) as a microbial sensor in epithelial and phagocytic cells that turns on inflammatory signals. Using a stem-cell-based "gut-in-a-dish" coculture model, we studied the interactions between microbes, epithelium and monocytes in the context of IBD. To mimic the in-vivo cell physiology, enteroid-derived monolayers (EDMs) were generated from the organoids isolated from WT and ELMO1-/- mice and colonic biopsies of IBD patients. The EDMs were infected with the IBD-associated microbes to monitor the inflammatory responses. ELMO1-depleted EDMs displayed a significant reduction in bacterial internalization, a decrease in pro-inflammatory cytokine productions and monocyte recruitment. The expression of ELMO1 is elevated in the colonic epithelium and in the inflammatory infiltrates within the lamina propria of IBD patients where the higher expression is positively correlated with the elevated expression of pro-inflammatory cytokines, MCP-1 and TNF-α. MCP-1 is released from the epithelium and recruits monocytes to the site of inflammation. Once recruited, monocytes require ELMO1 to engulf the bacteria and propagate a robust TNF-α storm. These findings highlight that the dysregulated epithelial ELMO1→MCP-1 axis can serve as an early biomarker in the diagnostics of IBD and other inflammatory disorders.

作者列表:["Prathapan KM","Ramos Rivers C","Anderson A","Koutroumpakis F","Koutroubakis IE","Babichenko D","Tan X","Tang G","Schwartz M","Proksell S","Johnston E","Hashash JG","Dunn M","Wilson A","Barrie A","Harrison J","Hartman D","Kim SC","Binion DG"]

METHODS:BACKGROUND:Peripheral blood eosinophilia (PBE) is a biomarker of an aggressive multiyear natural history in adults with inflammatory bowel diseases (IBDs). Additionally, PBE at diagnosis is associated with higher disease activity in pediatric-onset IBD. We sought to determine if PBE can function as a biomarker of long-term disease severity in pediatric-onset IBD patients who are followed into adulthood. METHODS:We analyzed a consented, prospective, natural history IBD registry at an adult tertiary center from 2009 to 2018. Prevalence of PBE was evaluated in both pediatric- and adult-onset IBD patients. Demographics, clinical characteristics, and health care utilization data were compared in patients with and without PBE. RESULTS:Among 2800 adult IBD patients, 23.4% had pediatric-onset disease. PBE was found in 34% of the pediatric-onset patients compared with 26.8% of the adult-onset IBD patients (P < 0.001). In the pediatric-onset IBD cohort, PBE was associated with higher rates of allergies (P < 0.0001), but not of asthma, allergic rhinitis, or primary sclerosing cholangitis. In the adult IBD patients with pediatric-onset disease, PBE was associated with higher rates of C-reactive protein elevation (P < 0.0001), erythrocyte sedimentation rate elevation (P < 0.0001), higher health care utilization, and higher average health care charges per year (P < 0.00001). CONCLUSIONS:Peripheral blood eosinophilia was more prevalent in adult IBD patients with pediatric-onset compared with adult-onset disease. Among all IBD patients with long-term follow-up, PBE defined a subgroup with more severe illness. These data suggest that PBE may be a biomarker for a high-risk subgroup with high cost trajectory and long-term severity in pediatric-onset IBD that persists into adulthood.

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作者列表:["Ronchetti S","Gentili M","Ricci E","Migliorati G","Riccardi C"]

METHODS::Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a complex pathogenesis, affecting people of all ages. They are characterized by alternating phases of clinical relapse and remission, depending on the fine balance between immune cells and the gut microbiota. The cross talk between cells of the immune system and the gut microbiota can result in either tolerance or inflammation, according to multifactorial triggers, ranging from environmental factors to genetic susceptibility. Glucocorticoid (GC) administration remains the first-line treatment for IBDs, although long-term use is limited by development of serious adverse effects. Recently, new alternative pharmacological therapies have been developed, although these are not always effective in IBD patients. There is a constant demand for effective new drug targets to guarantee total remission and improve the quality of life for IBD patients. The glucocorticoid-induced leucine zipper (GILZ) has been implicated as a promising candidate for this purpose, in view of its powerful anti-inflammatory effects that mimic those of GCs while avoiding their unwanted adverse reactions. Here we present and discuss the latest findings about the involvement of GILZ in IBDs.

关键词: GILZ IBD 自身免疫 炎症
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